title: Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: a case-control observational study based on registry data.
abstract: Patients with long-standing inflammatory bowel disease (IBD) have an increased risk for colorectal carcinoma (CRC). Earlier studies suggest that the severity of inflammation is an independent risk factor for CRC in ulcerative colitis (UC). We investigated the role of histological inflammation as a risk factor for colorectal dysplasia or CRC to better target dysplasia surveillance in IBD. By combining our hospital patient registry and pathology database between 1996 and 2008, we identified 183 IBD patients with dysplasia or CRC. The control group was collected from our registry of IBD patients. Histological severe inflammation was present in 41.4% of patients with dysplasia and in 24.1% of patients with CRC, but in only 4.3% of controls. Severe inflammation had an odds ratio (OR) of 31.8 [95% confidence interval (CI): 15.6-64.9] for dysplasia or carcinoma compared to patients with no inflammation. Among patients with mild to moderate inflammation, the OR was 2.6 (95% CI: 1.6-4.1). Disease duration increased the annual risk for dysplasia or CRC by 4.5%. Coexisting primary sclerosing cholangitis (PSC) did not elevate the risk, whereas use of thiopurines (OR = 0.09, 95% CI: 0.02-0.33) and also 5-aminosalicylic acid (OR 0.17, 95% CI: 0.017-1.01) protected against CRC. As conclusion, degree of inflammation and duration of disease cumulatively increase the risk for dysplasia and CRC. PSC was not identified as a risk factor. We demonstrated that use of thiopurines strongly protects against CRC. These results can be applied to better target dysplasia surveillance in IBD patients.
authors.affiliation: Clinic of Gastroenterology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Urpo
authors.initials: U
authors.lastname: Nieminen
authors.forename: Airi
authors.initials: A
authors.lastname: Jussila
authors.forename: Stig
authors.initials: S
authors.lastname: Nordling
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.forename: Martti A
authors.initials: MA
authors.lastname: Färkkilä
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000453:epidemiology* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D015179:Colorectal Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine
keywords: colorectal carcinoma; disease duration; epithelial dysplasia; inflammation activity; inflammatory bowel disease; risk factors